Identification and Characterization of RK22, a Novel Antimicrobial Peptide from Hirudinaria manillensis against Methicillin Resistant Staphylococcus aureus

Staphylococcus aureus (S. aureus) infections are a leading cause ofmorbidity andmortality, which are compounded by drug resistance. Bymanipulating the coagulation system, S. aureus gains a significant advantage over host defense mechanisms, with hypercoagulation induced by S. aureus potentially aggravating infectious diseases. Recently, we and other researchers identified that a higher level of LL-37, one endogenous antimicrobial peptide with a significant killing effect on S. aureus infection, resulted in thrombosis formation through the induction of platelet activation and potentiation of the coagulation factor enzymatic activity. In the current study, we identified a novel antimicrobial peptide (RK22) from the salivary gland transcriptome of Hirudinaria manillensis (H. manillensis) through bioinformatic analysis, and then synthesized it, which exhibited good antimicrobial activity against S. aureus, including a clinically resistant strain with a minimal inhibitory concentration (MIC) of 6.25 mu g/mL. The RK22 peptide rapidly killed S. aureus by inhibiting biofilm formation and promoting biofilm eradication, with good plasma stability, negligible cytotoxicity, minimal hemolytic activity, and no significant promotion of the coagulation system. Notably, administration of RK22 significantly inhibited S. aureus infection and the clinically resistant strain in vivo. Thus, these findings highlight the potential of RK22 as an ideal treatment candidate against S. aureus infection.

Automated summary

Staphylococcus aureus (S. aureus) infections are a leading cause of morbidity and mortality, and drug resistance worsens their severity. Researchers have discovered a new antimicrobial peptide called RK22 that exhibits good antibacterial activity against S. aureus, rapidly killing the bacteria without exacerbating the coagulation system. In in vivo experiments, RK22 significantly inhibited S. aureus infection, including a clinically resistant strain, making it a potential candidate for the treatment of S. aureus infections.